Citations

HappiGenius is a mindfulness-based social–emotional learning (SEL) program developed and initially deployed in the context of COVID-19. Novel features of the HappiGenius program include the use of behavioral practice and activities to enhance traditional classroom-based learning, the capability to teach in a remote setting, and a focus on internalizing behaviors in addition to traditionally targeted externalizing behaviors. A pilot study of four third-grade classrooms completed in the previous academic year showed promising results for improvements in students’ experience of positive affect, self-compassion, total difficulties, and prosocial behaviors. This quasi-experimental case-control study was conducted in 14 third-grade classrooms across four schools in a midsize Midwestern US city. We hypothesized that HappiGenius would lead to improvements in positive affect, self-compassion, and mindfulness, in addition to other social behaviors measured by quantitative standardized scales. We used qualitative methodology to determine whether HappiGenius was feasible and acceptable to teachers for use in the classroom. While there was no statistically significant change in positive affect, self-compassion, or mindfulness, there was meaningful improvement in student internalizing problems and peer problems. Analysis of qualitative data showed the importance of timing during the year to maximize classroom benefits like establishing behavioral expectations early and reducing problem behaviors. The study represents a step in the direction of evaluating the implementation and outcomes of a new social–emotional learning program developed with deliberate attention to internalizing problems alongside traditionally studied externalizing problems.

Leptomeningeal disease (LMD) is a devastating sequelae of metastatic spread that affects approximately 5% of cancer patients. The incidence of LMD is increasing due to advancements in systemic therapy and enhanced detection methods. The purpose of this review is to provide a detailed overview of the evidence in the detection, prognostication, and treatment of LMD. A comprehensive literature search of PUBMED was conducted to identify articles reporting on LMD including existing data and ongoing clinical trials. We found a wide array of treatment options available for LMD including chemotherapy, targeted agents, and immunotherapy as well as several choices for radiotherapy including whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and craniospinal irradiation (CSI). Despite treatment, the prognosis for patients with LMD is dismal, typically 2–4 months on average. Novel therapies and combination approaches are actively under investigation with the aim of improving outcomes and quality of life for patients with LMD. Recent prospective data on the use of proton CSI for patients with LMD have demonstrated its potential survival benefit with follow-up investigations underway. There is a need for validated metrics to predict prognosis and improve patient selection for patients with LMD in order to optimize treatment approaches.

Soft tissue aneurysmal bone cysts (STABCs) are rare neoplasms histopathologically identical to aneurysmal bone cysts. These benign lesions are characterized by thin, peripheral ossification and no skeletal continuity. STABC may be difficult to distinguish from myositis ossificans (MO) and malignant entities from imaging and fine needle aspiration, due to rarity and overlapping features. We present a case of a STABC occurring in the paraspinal cervical muscles. The imaging, histopathology, molecular analysis, and treatment are discussed. Four other published cases of STABC of the head and neck are reviewed.

BACKGROUND: Concerns persist regarding the effectiveness of robotic proctectomy compared with open proctectomy for locally advanced rectal cancer with a high risk of circumferential resection margin involvement. OBJECTIVE: Comparison of surrogate cancer outcomes after robotic versus open proctectomy in this subpopulation. DESIGN: Retrospective cohort study. SETTING: Three academic hospitals (Mayo Clinic Arizona, Florida, and Rochester) with data available through the Mayo Data Explorer platform. PATIENTS: Patients at high risk of circumferential resection margin involvement were selected on the basis of the MRI-based definition from the MERCURY I and II trials. MAIN OUTCOME MEASURES: Rate of pathologic circumferential resection margin involvement (≤1 mm), mesorectal grading, and rate of distal margin involvement. RESULTS: Out of 413 patients, 125 (30%) underwent open and 288 (70%) underwent robotic proctectomy. Open proctectomy was significantly associated with a greater proportion of cT4 tumors (39.3% vs 24.8%, p = 0.021), multivisceral/concomitant resections (40.8% vs 18.4%, p < 0.001), and less frequent total neoadjuvant therapy use (17.1% vs 47.1%, p = 0.001). Robotic proctectomy was less commonly associated with pathologic circumferential resection margin involvement (7.3% vs 17.6%, p = 0.002), including after adjustment for cT stage, neoadjuvant therapy, and multivisceral resection (OR 0.326; 95% CI, 0.157–0.670, p = 0.002). Propensity score matching for 66 patients per group and related multivariable analysis no longer indicated any reduction of circumferential positive margin rate associated with robotic surgery ( p = 0.86 and p = 0.18). Mesorectal grading was comparable (incomplete mesorectum in 6% robotic proctectomy patients vs 11.8% open proctectomy patients, p = 0.327). All cases had negative distal resection margins. LIMITATION: Retrospective design. CONCLUSIONS: In patients with locally advanced rectal cancer at high risk of circumferential resection margin involvement, robotic proctectomy is an effective approach and could be pursued when technically possible as an alternative to open proctectomy. See Video Abstract . RESULTADOS COMPARATIVOS ENTRE LA PROCTECTOMÍA ROBÓTICA Y LA PROCTECTOMÍA ABIERTA EN CASOS DE CÁNCER DE RECTO CON ALTO RIESGO DE MÁRGEN DE RESECCIÓN CIRCUNFERENCIAL POSITIVO ANTECEDENTES: Persisten preocupaciones con respecto a la efectividad de la proctectomía robótica en comparación con la proctectomía abierta en casos de cáncer de recto localmente avanzado con un alto riesgo de margen de resección circunferencial positivo. OBJETIVO: Comparar los resultados en la subpoblación de portadores de cáncer luego de una proctectomía robótica versus una proctectomía abierta. DISEÑO: Estudio retrospectivo de cohortes. AJUSTE: Realizado en tres hospitales académicos (Mayo Clinic de Arizona, Florida y Rochester) a través de la plataforma Mayo Data Explorer. PACIENTES: Fueron seleccionados aquellos pacientes con alto riesgo de compromiso sobre el margen de resección circunferencial, según la definición de los Estudios Mercury I-II basada en la Imágen de Resonancia Magnética. MEDIDAS DE RESULTADO PRINCIPALES Y SECUNDARIAS: La tasa de compromiso patológico sobre el margen de resección circunferencial (≤1 mm), la clasificación mesorrectal y la tasa del compromiso del margen distal. RESULTADOS: De 413 pacientes, 125 (30%) fueron sometidos a una proctectomía abierta y 288 (70%) a proctectomía robótica. La proctectomía abierta se asoció significativamente con una mayor proporción de tumores cT4 (39,3% frente a 24,8%, p = 0,021), las resecciones multiviscerales/concomitantes fueron de 40,8% frente a 18,4%, p < 0,001 y una adminstración menos frecuente de terapia neoadyuvante total (17,1). % vs 47,1%, p = 0,001). La proctectomía robótica se asoció con menos frecuencia con la presencia de una lesión sobre el margen de resección circunferencial patológico (7,3% frente a 17,6%, p = 0,002), incluso después del ajuste por estadio cT, de la terapia neoadyuvante y de resección multivisceral (OR 0,326, IC 95% 0,157-0,670, p = 0,002). El apareado de propensión por puntuación en 66 pacientes por grupo y el análisis multivariable relacionado, no mostraron ninguna reducción en la tasa de margen positivo circunferencial asociado con la cirugía robótica ( p = 0,86 y p = 0,18). La clasificación mesorrectal fue igualmente comparable (mesorrecto incompleto en el 6% de los pacientes con RP frente al 11,8% de los pacientes con OP, p = 0,327). Todos los casos tuvieron márgenes de resección distal negativos. LIMITACIÓN: Diseño retrospectivo. CONCLUSIÓN: En pacientes con cáncer de recto localmente avanzado con alto riesgo de compromiso del margen de resección circunferencial, la proctectomía robótica es un enfoque eficaz y podría realizarse cuando sea técnicamente posible como alternativa a la proctectomía abierta. (Traducción—Dr. Xavier Delgadillo )

Abstract Background Cardiac sarcoidosis (CS) is a granulomatous disease that can manifest as conduction defects, ventricular arrhythmias, and heart failure. The diagnosis of CS is inherently difficult due to variable presentations; as such, endomyocardial biopsy is often required but lacks sensitivity due to patchy myocardial involvement. Moreover, the diagnostic criteria of CS and arrhythmogenic cardiomyopathy overlap, particularly in right-side dominant or biventricular presentations, which further complicates an already challenging differential diagnosis. Case summary A 53-year-old man with no prior chronic medical conditions presented with ventricular tachycardia (VT) and heart failure with reduced ejection fraction. He was found to have biventricular cardiomyopathy and late gadolinium enhancement on cardiac magnetic resonance imaging, resulting in an initial diagnosis of arrhythmogenic cardiomyopathy. Implantable cardioverter-defibrillator was placed, but he was readmitted for recurrent VT 2 months later. Despite an aggressive VT therapy (combination of antiarrhythmic drugs, epicardial and endocardial ablation, and stellate ganglion block), he continued with refractory VT and developed cardiogenic shock. Extra-corporeal membrane oxygenation was initiated as a bridge to heart transplantation. Pathology of the explanted heart revealed the underlying disease to be CS. Discussion Cardiac sarcoidosis can mimic arrhythmogenic biventricular cardiomyopathy and may be difficult to distinguish by the proposed diagnostic criteria. High clinical suspicion and thorough investigation are necessary for an earlier diagnosis and initiation of treatment.

Importance Plasma biomarkers show promise for identifying Alzheimer disease (AD) neuropathology and neurodegeneration, but additional examination among diverse populations and throughout the life course is needed. Objective To assess temporal plasma biomarker changes and their association with all-cause dementia, overall and among subgroups of community-dwelling adults. Design, Setting, and Participants In 1525 participants from the US-based Atherosclerosis Risk in Communities (ARIC) study, plasma biomarkers were measured using stored specimens collected in midlife (1993-1995, mean age 58.3 years) and late life (2011-2013, mean age 76.0 years; followed up to 2016-2019, mean age 80.7 years). Midlife risk factors (hypertension, diabetes, lipids, coronary heart disease, cigarette use, and physical activity) were assessed for their associations with change in plasma biomarkers over time. The associations of biomarkers with incident all-cause dementia were evaluated in a subpopulation (n = 1339) who were dementia-free in 2011-2013 and had biomarker measurements in 1993-1995 and 2011-2013. Exposure Plasma biomarkers of amyloid-β 42 to amyloid-β 40 (Aβ42:Aβ40) ratio, phosphorylated tau at threonine 181 (p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) were measured using the Quanterix Simoa platform. Main Outcomes and Measures Incident all-cause dementia was ascertained from January 1, 2012, through December 31, 2019, from neuropsychological assessments, semiannual participant or informant contact, and medical record surveillance. Results Among 1525 participants (mean age, 58.3 [SD, 5.1] years), 914 participants (59.9%) were women, and 394 participants (25.8%) were Black. A total of 252 participants (16.5%) developed dementia. Decreasing Aβ42:Aβ40 ratio and increasing p-tau181, NfL, and GFAP were observed from midlife to late life, with more rapid biomarker changes among participants carrying the apolipoprotein E epsilon 4 ( APOE ε4) allele. Midlife hypertension was associated with a 0.15-SD faster NfL increase and a 0.08-SD faster GFAP increase per decade; estimates for midlife diabetes were a 0.11-SD faster for NfL and 0.15-SD faster for GFAP. Only AD-specific biomarkers in midlife demonstrated long-term associations with late-life dementia (hazard ratio per SD lower Aβ42:Aβ40 ratio, 1.11; 95% CI, 1.02-1.21; per SD higher p-tau181, 1.15; 95% CI, 1.06-1.25). All plasma biomarkers in late life had statistically significant associations with late-life dementia, with NfL demonstrating the largest association (1.92; 95% CI, 1.72-2.14). Conclusions and Relevance Plasma biomarkers of AD neuropathology, neuronal injury, and astrogliosis increase with age and are associated with known dementia risk factors. AD-specific biomarkers’ association with dementia starts in midlife whereas late-life measures of AD, neuronal injury, and astrogliosis biomarkers are all associated with dementia.

Importance Outcomes for patients with unresectable stage III non–small cell lung cancer (NSCLC) treated with chemoradiation therapy (CRT) have improved with adjuvant immune checkpoint inhibitors, with a reported 5-year overall survival benefit of approximately 10% for adjuvant durvalumab vs placebo after completion of CRT without progression and with preserved performance status. Starting atezolizumab prior to CRT may allow more patients to benefit from immunotherapy. Objective To evaluate clinical outcomes of patients treated with atezolizumab before and after CRT for unresectable stage III NSCLC. Design, Setting, and Participants This single-cohort, phase II, nonrandomized controlled trial was conducted at 11 US sites. Patients with pathologically confirmed, unresectable stage III NSCLC who were treatment naive and had good performance status were enrolled between January 3, 2018, and July 24, 2019. Data were locked on March 21, 2023. Interventions Patients received four 21-day cycles of atezolizumab, 1200 mg intravenously, with therapy administered on day 1 of each cycle. Patients not experiencing tumor progression continued to CRT (60 Gy to involved fields) concurrent with weekly carboplatin area under the curve of 2 and paclitaxel, 50 mg/m 2 , followed by planned consolidation carboplatin area under the curve of 6 and paclitaxel, 200 mg/m 2 , for two 21-day cycles. Patients not experiencing progression continued atezolizumab, 1200 mg, every 21 days to complete 1 year of therapy. Main Outcomes and Measures The primary end point was the disease control rate at 12 weeks. Secondary end points were progression-free survival, overall survival, overall response rate, safety, and translational science end points. Results A total of 62 patients (median [range] age, 63.9 [38.1-86.5] years; 32 female [51.6%]) were enrolled and received at least 1 dose of atezolizumab. The disease control rate at 12 weeks was 74.2% (80% CI, 65.7%-81.4%). Median progression-free survival was 30.0 months (95% CI, 15.8 to not evaluable), and the median overall survival was not reached. The overall survival rate at 24 months was 73.7% (95% CI, 63.4%-85.7%), and the overall response rate was 66.2%. Seventeen patients (27.4%) experienced grade 3 or higher immune-related adverse events, including 1 with grade 5 pneumonitis and 1 with grade 4 Guillain-Barré syndrome. Thirty patients (48.4%) experienced grade 3 or higher treatment-related adverse events. Conclusions and Relevance These findings suggest that neoadjuvant atezolizumab merits further study based on safety and encouraging outcomes. Trial Registration ClinicalTrials.gov Identifier: NCT03102242

The demand for telehealth services in the United States saw an unprecedented increase following the 2020 COVID-19 pandemic. Prior to the pandemic, intake and virtual rooming functions for scheduled, synchronous video appointments at Mayo Clinic were supported by a small centralised team of virtual agents within its Center for Connected Care (Connected Care). In response to the pandemic-generated demand, Connected Care leveraged its existing model and the support of temporary staff to rapidly scale support for the increased video visit demand across the enterprise. Once demand stabilised in the summer of 2020, Mayo Clinic’s destination medical centres in Minnesota, Florida and Arizona, and Mayo Clinic Health System’s sites in the Midwest, launched pilots to evaluate alternative telehealth delivery models. The goal of these pilots was to test the flexibility of alternative intake models for supporting long-term scalability and growth. Through these pilots, each site developed unique workflows and staffing plans with the overall intake function remaining standardised across all locations. The workflows delineated responsibilities between clinical departments and virtual agents, leveraged current infrastructure and maximised best practices from the original model. This paper outlines the models implemented, and presents lessons learned and best practices garnered from each implementation.